Yang Ming, Xu San-peng, Ao Qi-lin
Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Zhonghua Bing Li Xue Za Zhi. 2013 Apr;42(4):257-61. doi: 10.3760/cma.j.issn.0529-5807.2013.04.010.
To investigate the expression of fatty acid synthase (FAS) in adenosis, atypical ductal epithelial hyperplasia, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of breast, and the correlation of FAS expression with HER2 gene amplification in IDC.
Immunohistochemical EnVision method staining for FAS was performed in 100 cases of breast lesions and 10 normal breast tissues. HER2 gene amplification was detected with FISH in 60 cases of IDC.
The cohort included 10 cases of adenosis, 10 atypical ductal epithelial hyperplasia, 20 DCIS (8 high-grade, 9 intermediated-grade and 3 low-grade), and 60 cases of IDC (5 grade 1, 40 grade 2 and 15 grade 3). FAS expression was negative in all 10 normal breast tissues; in the 10 cases of adenosis, strongly positive FAS expression was detected in one case, positive in 2, weakly positive in 4, and negative in 3; in the 10 cases of atypical ductal epithelial hyperplasia, FAS immunohistochemistry showed that 1 was strongly positive, 4 positive, 4 weakly positive, and 1 negative; in the 20 cases of DCIS, FAS immunostaining showed that 12 were strongly positive, 5 positive, 1 weakly positive, and 2 negative; FAS expression showed a clear increasing trend from normal breast tissue, atypical ductal epithelial hyperplasia to DCIS (χ(2) = 42.02, P < 0.01). Likewise, the increasing trend was also demonstrated from adenosis to DCIS (χ(2) = 34.69, P < 0.01). There was also a positive correlation between FAS expression and extent of lesion among normal breast tissue, adenosis, atypical ductal epithelial hyperplasia and DCIS (χ(2) = 86.02, P < 0.01; r = 0.568, P < 0.01). FAS expression was not correlated with the grade of DCIS (χ(2) = 9.12, P = 0.16). In the five cases of grade 1 IDC, FAS immunostaining showed that 4 cases were strongly positive and 1 positive; in the 40 cases of grade 2 IDC, FAS immunostaining showed that 27 strongly positive, 12 positive, and 1 negative; in the 15 cases of grade 3 IDC, FAS immunostaining showed that 6 were strongly positive, 5 positive, 3 weakly positive, and 1 negative; FAS expression was stronger and more extensive in DCIS, IDC grades 1 and 2 than that in other groups. However, FAS expression was weaker in the IDC grade 3 (χ(2) = 11.26, P = 0.01). The positive expression rate of FAS in IDC was generally higher than that in benign breast lesions (χ(2) = 47.19, P < 0.01). In the 60 cases of IDC, FISH showed HER2 gene amplification in 22 cases, but not in the remaining 38 cases. FAS expression in IDC was highly correlated with HER2 gene amplification (r = 0.44, P < 0.01). The expression of FAS had significant correlation with status of ER and PR and tumor size (P < 0.05). There was no significant correlation with age, immunohistochemical HER2 expression, lymph node metastasis and clinical stage (P > 0.05).
FAS may be closely related to the carcinogenesis of breast IDC. FAS expression is closely associated with HER2 gene amplification in IDC.
探讨脂肪酸合酶（FAS）在乳腺腺病、非典型导管上皮增生、导管原位癌（DCIS）及浸润性导管癌（IDC）中的表达情况，以及IDC中FAS表达与HER2基因扩增的相关性。
采用免疫组织化学EnVision法对100例乳腺病变组织及10例正常乳腺组织进行FAS染色。采用荧光原位杂交（FISH）法检测60例IDC中的HER2基因扩增情况。
该队列包括10例腺病、10例非典型导管上皮增生、20例DCIS（8例高级别、9例中级别、3例低级别）及60例IDC（5例1级、40例2级、15例3级）。10例正常乳腺组织中FAS表达均为阴性；10例腺病中，1例FAS强阳性，2例阳性，4例弱阳性，3例阴性；10例非典型导管上皮增生中，FAS免疫组化显示1例强阳性，4例阳性，4例弱阳性，1例阴性；20例DCIS中，FAS免疫染色显示12例强阳性，5例阳性，1例弱阳性，2例阴性；FAS表达从正常乳腺组织、非典型导管上皮增生到DCIS呈明显上升趋势（χ(2)=42.02，P<0.01）。同样，从腺病到DCIS也呈现上升趋势（χ(2)=34.69，P<0.01）。正常乳腺组织、腺病、非典型导管上皮增生及DCIS中FAS表达与病变程度也呈正相关（χ(2)=86.02，P<0.01；r=0.568，P<0.01）。FAS表达与DCIS分级无关（χ(2)=9.12，P=0.16）。5例1级IDC中，FAS免疫染色显示4例强阳性，1例阳性；40例2级IDC中，FAS免疫染色显示27例强阳性，12例阳性，1例阴性；15例3级IDC中，FAS免疫染色显示6例强阳性，5例阳性，3例弱阳性，1例阴性；DCIS、1级和2级IDC中FAS表达比其他组更强且更广泛。然而，3级IDC中FAS表达较弱（χ(2)=11.26，P=0.01）。IDC中FAS阳性表达率总体高于乳腺良性病变（χ(2)=47.19，P<0.01）。60例IDC中，FISH显示22例HER2基因扩增，其余38例未扩增。IDC中FAS表达与HER2基因扩增高度相关（r=0.44，P<0.01）。FAS表达与ER、PR状态及肿瘤大小有显著相关性（P<0.05）。与年龄、免疫组化HER2表达、淋巴结转移及临床分期无显著相关性（P>0.05）。
FAS可能与乳腺IDC的发生密切相关。IDC中FAS表达与HER2基因扩增密切相关。
